1. Field of the Invention
This invention relates generally to compositions with antimicrobial activity, and more specifically to compositions containing acid-solubilized copper-ammonium or acid-solubilized copper-zinc-ammonium complexes as active ingredients.
2. Description of Related Art
The antimicrobial effects of copper metal and copper salts have been known since ancient times. The role of copper as an anti-microbial agent was first described in the Smith Papyrus, an Egyptian medical text written around 2,600 BC, which describes the application of copper to sterilize chest wounds and drinking water.
The Greeks. Romans and Aztecs used copper metal or its compounds for the treatment of chronic infections and for hygiene in general. For example, in the Hippocratic Collection copper is recommended for the treatment of leg ulcers associated with varicose veins. To prevent infection of fresh wounds, the Greeks sprinkled a dry powder composed of copper oxide and copper sulfate on the wound. Another antiseptic wound treatment at the time was a boiled mixture of honey and red copper oxide. The Greeks had easy access to copper since the metal was readily available on the island of Kypros (Cyprus) from which the Latin name for copper, cuprum, is derived.
The Ancient Indian ayurvedic text Charaka Samhita (300 BC) also mentions how copper kills fatal microbes, including its role in the purification of drinking water. Pliny (23 to 79 A.D.) described a number of remedies involving copper, for example, black copper oxide was given with honey to remove intestinal worms.
In more modern times, the first observation of copper's role in the immune system was published in 1867 when it was reported that, during the cholera epidemics in Paris of 1832, 1849 and 1852, copper workers were immune to the disease. Further, animals deficient in copper have been shown to have increased susceptibility to bacterial pathogens such as Salmonella and Listeria. 
Copper sulfate is the key active component of the fungicidal “Bordeaux mixture” that was invented in the 19th century and is still used in agriculture today, as are numerous other copper-based agrochemicals.
Pathogenic microbes such as bacteria, fungi and viruses are responsible for many of the diseases in multicellular organisms as illustrated by the following non-limiting examples.
In the pharmaceutical area, bacterial infections are involved in skin diseases such as acne (Propionibacterium acnes) and eczema (Staphylococcus aureus). Healthcare-acquired infections (HAIs) caused by meticillin-resistant Staphylococcus aureus (MRSA), Acinetobacter sp. Klebsiella pneumonia (in which the NDM-1 enzyme gene was originally identified) and Legionella pneumophila which is the cause of Legionnaire's disease. Escherichia coli (E. coli) is a common cause of urinary tract infections. These and other HAIs are estimated to cause the death of nearly 100,000 people in the USA annually. Pathogenic E. coli 0157:117 causes gastroenteritis when ingested through contaminated food. Diseases caused by fungi may be relatively mild such as athlete's foot (Tricophyton sp.), dandruff (Malassezia globosa) and thrush (Candida albicans), but fungi such as Aspergillus fumigatus (A. fumigatus) and Candida albicans (C. albicans), and yeasts such as Cryptococcus neoformans may cause life-threatening infections in immune compromised patients. Viruses are also responsible for common diseases such as colds (Rhinoviruses) and influenza (Influenza viruses A. B and C) and cold sores (Herpes simplex virus), to more serious viral diseases such as rabies and ebola.
Bacterial infections of skin wounds such as pressure sores and diabetic leg ulcers can exacerbate the condition and copper salts and copper-based compositions have been shown to be effective against these diseases by virtue of both their anti-bacterial effects and their ability to stimulate wound healing by enhancing growth factor production.
In the cosmetic area, copper or copper-zinc compositions have been shown to be effective at, for example, ameliorating the effects of mild to moderate sunburn and mild burns, and also in reducing the itching and inflammation caused by insect bites and reducing the appearance of wrinkles.
In the agricultural area, fungal diseases are currently killing tanoaks in the western United States (Phytophthora ramorum) and ash trees in Europe (Chalara fraxinea). Fungal and bacterial diseases of grape vines, fruit and vegetable bearing plants and cereal crops are a threat to world food production.
The presence of increasing numbers of drug-resistant strains of pathogenic microbes in hospitals and in the general environment is becoming a great concern as illustrated by the following examples. Antibiotic-resistant and multi-drug resistant strains of pathogenic bacteria such as MRSA, vancomycin-resistant Staphylococcus aureus (VRSA). Acinetobacter baumannii. E. coli and Mycobacterium tuberculosis are now commonplace. Resistant strains of pathogenic fungi such as ketoconazole-resistant C. albicans and A. fumigatus are an increasing problem particularly in immune-compromised patients. Fungicide-resistant plant pathogenic fungi constantly evolve and require new anti-fungal agents for their treatment. For example, Phytophthora infestans, the cause of potato blight, became highly resistant to Metalaxyl in the late 20th century. Pathogenic viruses similarly develop resistance to anti-viral drugs, the development of resistance of the H1N1 “swine flu” influenza A strain to oseltamivir phosphate (TAMIFLU®, a registered trademark of Genentech. San Francisco, Calif. USA) in the past five years being a recent example.